Saturday, May 18, 2024

Researchers discover cancer-driving mechanism, develop drug to treat it

Dr. Josh Andersen, who heads Brigham Young University’s Fritz B. Burns Cancer Research Laboratory, discovered the mechanism by which a gene, called TNK1, becomes an oncogenic driver in cancer. TNK1 is present in all cells, but when mutated, it becomes dangerous and able to convert normal cells into cancer cells. This puts TNK1 in a select category of cancer driver genes. “You can think of cancer drivers as the engine that makes cancer grow and progress,” Andersen said. Andersen and colleagues also figured out how mutations in the TNK1 gene cause cancer. It’s a significant discovery considering only a handful of other drivers like TNK1 are known to scientists. For years, Andersen has studied a cancer-promoting protein called 14-3-3 that exists at unusually high levels within cancer cells. Six years ago, he identified TNK1 as an interacting partner of 14-3-3. His research, along with the research of Dr. Jeff Tyner at Oregon Health Sciences University, has led to a greater understanding of TNK1 and how it acts as a cancer driver. Andersen, Tyner, and other scientists shared research and data in a recently published article in the scientific journal Nature Communications. After identifying TNK1 six years ago, Andersen and several PhD students began working to understand its properties with the goal of designing and developing a new drug to treat tumors caused by TNK1. “Targeted therapy is the goal here,” said Andersen. “Being able to offer a cancer therapy that only targets the cancer driver – the engine making cancer grow – is going to help people live longer, healthier lives free from cancer. Targeted therapy holds the promise of being far more effective with fewer side effects than traditional chemotherapy and is revolutionizing cancer treatment.” Andersen contacted Dr. Steve Warner, senior vice-president and head of U.S. research at SDP Oncology, and asked him to help develop a drug to target TNK1. Warner, a BYU undergraduate classmate of Andersen’s. The years of research and data Andersen shared with SDP Oncology gave their researchers a great place to start. SDP Oncology scientists started designing compounds that would target TNK1 in cancer cells. Through computer modeling and structure-based rational design, they continued to test and then optimize how this compound would react. “We didn’t just design one drug and say, ‘Here it is!’,” said Warner. “Through trial and error, we would design and synthesize 20 or 30 potential candidate drugs and then evaluate those with different experiments in the lab. The results from those studies helped us understand how to improve the drug’s interaction with TNK1, and how to balance the need to retain other properties required for a viable drug. We went through these iterative rounds of optimization until we identified a drug that we could move forward with.” The pre-clinical results for the drug, called TP-5801, are promising. “We were very surprised how quickly we were able to find and optimize a development candidate for TNK1, which was enabled by the research Dr. Andersen had already done,” said Warner. “The pre-clinical data show that the drug is very promising with profound activity in models of cancer driven by TNK1.” The compound has passed FDA-required steps and is ready for what’s called a first-in-human study or Phase 1 clinical trial.

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